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Chapter 8: Control of Gene Expression

Epigenetic Inheritance

• DNA Methylation:

  • Mechanism that turns off genes by attracting proteins that bind to methylated cytosines, blocking gene transcription.

  • Methylation patterns are copied to daughter cells during DNA synthesis by maintenance methyltransferase.

• Histone Modification:

  • Histones from parent DNA are passed to daughter strands, carrying covalent modifications.

  • Enzymes modify nearby new histones, reestablishing chromatin patterns from parental chromosomes.

  • These mechanisms transmit gene expression patterns without altering the DNA sequence, a concept known as epigenetic inheritance.

  • Important for cellular memory and environmental response, with implications for diseases.

Post-Transcriptional Controls

• Definition: Controls regulating gene expression occurring after the beginning of transcription.

• Alternative RNA Splicing: Allows the production of different protein forms from the same gene.

• mRNA Stability and Translation:

  • mRNA's lifespan affects protein production; longer persistence leads to more protein output.

  • In bacteria, mRNAs degrade quickly (a few minutes) for rapid environmental adaptation; eukaryotic mRNAs generally last longer (e.g., β-globin mRNA ~10 hours).

  • Untranslated regions (UTRs) of mRNA regulate stability and translation efficiency through specific sequences attracting degradation proteins.

  • Eukaryotes use 5′ caps for ribosome guidance, while repressor proteins can inhibit translation initiation.

Regulatory RNAs

• MicroRNAs (miRNAs):

  • Small RNA molecules regulating gene expression by base-pairing with specific mRNAs, reducing their stability and translation.

  • Regulate ~1/3 of protein-coding genes; processed from precursor transcripts.

  • Packaged as RNA-induced silencing complex (RISC) to target and eliminate specific mRNAs.

• Small Interfering RNAs (siRNAs):

  • Arise from double-stranded foreign RNAs (viruses); part of the RNA interference (RNAi) defense mechanism.

  • Processed by Dicer (protein) into short fragments, incorporated into RISC, targeting and degrading specific foreign RNAs.

  • One mechanism of providing viral resistance within various organisms.

• Long Noncoding RNAs:

  • Larger RNAs (>200 nucleotides) possibly regulating gene activity in mammals; existence of ~8000 such RNAs.

  • Example: Xist, involved in X chromosome inactivation in females, promoting heterochromatin formation via coating and attracting silencing enzymes.

  • Some long noncoding RNAs arise from antisense transcripts, binding mRNAs and affecting their translation and stability.

Essential Concepts

• Eukaryotic cells express only a fraction of their genes, leading to differentiation in multicellular organisms.

• Gene expression can be regulated at various steps, but transcription initiation is usually the most critical control point.

• Transcription regulators bind to regulatory DNA sequences, activating or repressing transcription based on the DNA location relative to RNA polymerase binding sites.

• In eukaryotes, regulatory sequences can be separated from promoters by large distances.